Although obstructive sleep apnea has received the lion's share of recognition and investigation in research and practice, more troubling forms of sleep apnea, like those that are mediated by chemoreflex instability, exist and continue to have inadequate treatment. Central apneas and periodic breathing (now called the Cheyne Stokes breathing pattern) are the classic polysomnographic markers of strong chemoreflex modulation of sleep apnea. A recently described variant, "complex sleep apnea", demonstrates sustained induction of central apneas or severe periodic breathing during positive pressure titration for what seems to be obstructive disease on the diagnostic polysomnogram. The number of the affected population is large, especially when specific populations such as congestive heart failure are considered. It is estimated that complex sleep apnea alone makes up 10%-15% of the overall sleep apnea patient population or over 1.5 million patients (assuming a conservative estimate of $10 million overall sleep apnea population). In those with significant chemoreflex modulatory effects, the probability of failure of conventional positive airway pressure therapy is high. Positive airway pressure therapies tend to flush out and reduce the level of carbon dioxide (CO2);prevention of this hypocapnia state during the application of positive airway pressure therapies is an important stabilizing factor for chemoreflex-modulated sleep apnea syndromes. The Positive Airway Pressure Gas Modulator (PAPGAM), a new class of positive airway pressure device designed to prevent chemoreflex instability by carefully maintaining CO2 levels just above the CO2-dependent apneic threshold, has shown excellent acute results. Chronic effects with a modified dead space approach, called Enhanced Expiratory Rebreathing Space, have shown some success, but are less precise than directly controlling the CO2 level. This proposal will investigate the use of exhaled air to provide the CO2 that is mixed with the inlet air of the positive airway pressure device. By controlled mixing, we hope to completely eliminate the need for the high pressure tank, or at a minimum markedly increase its life. Thus, the aim is to obtain the precision of PAPGAM treatment but with reduced cost, marked improvements in ease of use, and minimized adverse outcomes from technical failures. The goals of the phase I research include: 1) building prototypes capable of diverting or pulling the exhaled air from the patient to the inlet of the positive airway pressure device;2) determining if a passive or an active rebreathing mechanism is required;3) determining what maximum concentrations are possible using each technique;and 4) clinically assessing the system. Successful implementation will result in a poweful new treatment for chemoreflex-modulated sleep apnea. PUBLIC HEALTH RELEVANCE: Abnormal control of breathing during sleep causes central or mixed forms of sleep apnea and is especially common in heart failure and kidney failure patients. The usual treatment for obstructive sleep apnea, a mask and air pressure device, does not work well in those with central / mixed sleep apnea. Recent research indicates that the air pressure device decreases the normal level of carbon dioxide and excellent treatment results have been achieved by increasing carbon dioxide levels back to normal levels. The proposed research will develop methods to use carbon dioxide exhaled by the patient to provide stability of breathing patterns during sleep. Success in development of this device, called the Positive Airway Pressure Rebreathing Modulator (PAPREM, to be used with air pressure treatments) will markedly improve treatment of complicated forms of sleep apnea.